Despite evidence of varying vaccine effectiveness, T cell responses to rotavirus (RV) vaccines remain incompletely studied. To address this research gap, RV-specific T cells in the blood of infants pre- and post-monovalent RV vaccination (RV1) were analyzed for memory recall and functionality using RV-specific peptide pool stimulation. We find that RV vaccine elicits heterogenous responses with respect to cellular and humoral immunity. T cell responses to RV vaccine are detectable in the periphery, though poorly functional. Vaccination induces Th2-biased conventional effector memory and central memory CD4 + T cells, as suggested by chemokine receptor profiles, though the response wanes by 8 months post vaccination. The presence of preexisting immunity results in no significant increase in either RV-specific IgA or T cells after vaccination. Our data provides the first in-depth assessment of RV-specific T cell responses induced by vaccine, demonstrating patterns of negative and positive association with response that may play a role in protection against rotavirus disease.

Data on MPXV-specific T-cell responses at the single-peptide level remain limited in patients with mpox and in MVA-BN vaccinees. Here, we characterized the breadth and specificity of MPXV-specific T-cell responses at the single-peptide level after in vitro expansion with overlapping 20-mer peptides spanning the MPXV proteins H3L, A35R, and B6R. The study included 28 adult males: 15 with a history of mpox (including 6 with additional MVA-BN vaccination), 7 MVA-BN-only vaccinees, and 6 unexposed participants. All mpox and MVA-BN participants responded to at least one H3L peptide, indicating broad immunogenicity, while responses to A35R and B6R were more common in the mpox group. Notably, the breadth of B6R-specific CD4+ T-cell responses correlated with hybrid immunity (r = 0.6; p = 0.02). Interestingly, MVA-BN and mpox individuals demonstrated distinct immunodominant patterns: H3L_251-270 and H3L_211-230 were mainly recognized among mpox individuals, whereas MVA-BN recognized H3L_221-240 more frequently. High-affinity HLA binding to multiple H3L peptides suggests broad population coverage. Additional immunogenetic analysis revealed a shared TRBV15 clonotype in about 50% of mpox cases. In summary, these findings highlight H3L as a potential vaccine target, guiding the development of next-generation multi-antigen MPXV vaccines to elicit comprehensive T-cell immunity.

The Immune Epitope Database (IEDB, iedb.org) has manually curated epitope data from over 26,000 publications across two decades. With PubMed adding ~5,000 articles daily, traditional curation methods face scalability challenges. Given the multimodality of data contained in scientific papers, we have sought to build an open-source vision language model (VLM)-based tool that human curators can use to speed up and automate biological data curation. Here we present a multimodal document ingestion and Question-Answering (QnA) pipeline that ties traditional Optical Character Recognition (OCR) and text matching with Vision-Language Model (VLM) capabilities. The system, which we call EPITOME, implements three-stage processing: regex-based epitope and MHC molecule identification, visual element extraction from PDFs, and contextual indexing that links peptide sequences, MHC molecules, and assays to their locations across text, tables, and figures. This indexing is used to supply context for further VLM QnA. Our preliminary results from EPITOME demonstrate promising zero-shot performance of open-source VLMs that suggest promise for accelerating biocuration through a curator-in-the-loop process, with our evaluation identifying strategic points where curator-in-the-loop intervention can enhance overall system accuracy.

Abstract Emerging evidence suggests that immunogenic cancer antigens may originate from the "dark genome", which comprises non-coding regions, alternative open reading frames (ORF), and untranslated regions (UTR), traditionally excluded from most neoepitope prediction pipelines. Consequently, systematic identification and validation of these noncanonical antigens has been technically challenging. To address this gap, we leveraged PEPMatch, a high-throughput peptide search tool, integrated with the Cancer Epitope Database and Analysis Resource (CEDAR) to systematically identify noncanonical sources of experimentally validated neoepitopes. We compiled seven comprehensive human databases encompassing both canonical and noncanonical protein sources: UniProtKB (human reference proteome with isoforms), UniParc (UniProt protein archive), Ensembl canonical proteins (ENSP), validated non-canonical ORFs (ncORF), and three-frame translations of complementary DNAs (cDNA) and non-coding RNAs (ncRNA), and six-frame translations of full gene sequences, including UTRs and introns (ENSG). Using PEPMatch's exact matching algorithm, we performed searches of 28,601 CEDAR neopeptides tested in 40,800 T cell assays against all seven databases. To validate our pipeline, we first analyzed 840 MHC class I cryptic neopeptides found by mass spectrometry, achieving a total mapping success of 98.33% using a sequential attribution search that revealed an enrichment in noncanonical sources (ncORF: 14.76%, cDNA: 41.55%, ncRNA: 4.76%, ENSG: 1.67%). Out of these cryptic neoepitopes, 5.60% were found in the human reference proteome and 28.93% in the UniParc database prior to the noncanonical sources. Applying this methodology to all 28,601 CEDAR's neopeptides revealed that 1.91% originated from noncanonical sources. We then focused on the relevant subset of 6,394 positive neoepitopes with confirmed immunogenicity from T cell assays. Notably, a significant percentage of these immunogenic positive neoepitopes mapped to noncanonical databases compared with the negative peptides (ncORF: 0.1% vs 0.0%, cDNA: 8.8% vs 2.6%, ncRNA: 1.4% vs 0.6%, ENSG: 3.4% vs 1.5%), suggesting that the 'dark genome' is a source of targetable neoepitopes. The specificity of this mapping approach was validated using randomly shuffled peptide controls, which yielded <1% spurious matches. These findings demonstrate that PEPMatch successfully identifies noncanonical genomic origins of cancer neoepitopes at scale given the appropriately curated database sources. CEDAR is implementing this annotation pipeline to provide researchers with mappings for dark genome antigens, enabling validation and discovery of unconventional targets for immunotherapy development. This work expands the targetable landscape of cancer immunotherapy by systematically cataloging epitopes from previously overlooked genomic regions. Citation Format: Daniel Marrama, Ibel Carri, Nina Blazeska, Randi Vita, Hannah K. Carter, Morten Nielsen, Alessandro Sette, Zeynep Kosaloglu-Yalcin, Bjoern Peters. Identifying noncanonical sources of cancer neoepitopes using PEPMatch and CEDAR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 47.

The first workshop dedicated to Lassa virus–specific correlates of protection (CoP) was held in 2024 and was convened by the Coalition for Epidemic Preparedness Innovations (CEPI). Experts from multiple disciplines reviewed existing knowledge and identified gaps in understanding Lassa virus- and vaccine-induced immune responses. Discussions covered key areas including epidemiology, immunogenicity, preclinical and clinical research, data science, and regulatory considerations, with the goal of pinpointing opportunities to discover CoP.

Paramyxoviruses comprise a diverse family of viruses that threaten global human health through direct infection and zoonotic transmission. Understanding adaptive immune responses to these viruses is critical for characterizing host-pathogen interactions and evaluating vaccine performance. Here, we systematically map human CD4+ T cell epitopes across Nipah and measles viruses, two prototypic members of the Paramyxoviridae family. We identify broad epitope repertoires, including 186 Nipah and 288 measles epitopes recognized in multiple donors. Epitopes are characterized for HLA binding and inferred restrictions, and broader HLA binding correlates with immunodominance. We observe overlapping T cell targets between viruses, with N and F proteins immunodominant in both and L additionally dominant in Nipah. We define conserved T cell epitope regions (CTERs) in Nipah virus that encompass 17% of the proteome, capture over 50% of T cell responses, show high conservation across different Henipaviruses, and elicit broadly cross-reactivity, supporting broad population coverage.

Tissue-resident immunity mediates host defense against pathogens and enables rapid adaptive memory responses. However, the study of tissue-resident immunity is hindered by a singular lack of experimental systems allowing pathogenic epithelial infection amidst the full spectrum of endogenous immune subsets. Particularly in lung, differing notions of transient versus sustained residency of tissue-resident memory T cells (TRM) have questioned the extent to which recall immunity to respiratory pathogens occurs locally or in concert with secondary lymphoid organs. We thus generated long-term adult human distal lung organoids from intact tissue fragments in 3D air-liquid interface (ALI) culture that co-preserved epithelial and stromal architecture alongside endogenous lung-resident immune cells (T, B, NK, myeloid). The organoid T cells exhibited persistent cytokine-assisted maintenance, expressed residency and memory markers, and preserved T cell receptor (TCR) repertoires of cognate fresh tissue. SARS-CoV-2 vigorously infected the organoid lung epithelium, stimulated inflammatory cytokine production, and crucially, induced widespread SARS-CoV-2-specific, tissue-resident T cell responses. Our studies introduce a robust adult human lung organoid experimental system containing a physiologic air interface and diverse resident immune subsets, demonstrate the organ-autonomous sufficiency of lung pathogen memory T cell responses, distinct from secondary lymphoid tissue, and provide a platform to investigate tissue-resident immunity in health and disease.

Background: We investigated discordant SARS-CoV-2 infection outcomes among household contacts. Methods: 95 recently-exposed household contacts were recruited from June 2020 to February 2023 in a prospective study of ''discordant pairs'', where one individual experienced documented SARS-CoV-2 infection while another close contact consistently tested negative despite shared living arrangements. We collected pre- and post-infection samples and analyzed both SARS-CoV-2 and common cold coronavirus (CCC)-specific T cell responses, as well as spike RBD neutralizing and nucleocapsid-binding antibody titers. Results: Antibody and cellular immune responses did not identify a single predominant mechanism explaining discordant outcomes. Instead, we observed distinct immunological patterns that could be associated with protection from infection across different household contacts. In ∼40 % of cases, uninfected individuals showed pre-existing immunity to non-spike antigens and CCC sequences. Moreover, 30 % of uninfected individuals displayed evidence suggestive of abortive infections, characterized by increased T responses without detectable changes in antibody levels. The remaining cases showed no clear changes in immunological patterns. Conclusions: Multiple immunity-associated factors operate in household settings for SARS-CoV-2-exposed individuals who do not develop overt infection, including both pre-existing immunity and abortive or transient infections. Although causality cannot be established without additional functional assays, this diversity of protective immune responses might help explain why some individuals remain uninfected despite close contact with SARS-CoV-2-positive household members.

Abstract Introduction Cytomegalovirus (CMV) is a leading cause of congenital birth defects and has a substantial clinical impact on a significant proportion of the U.S. population. To date, no approved vaccines are available to prevent congenital CMV infection in humans. Our study aimed to delineate specific immunogenic regions within each ORF through peptide deconvolution. Methods In a cohort of 27 CMV-positive donors, we examined T-cell memory responses across a set of 31 open reading frames (ORFs). We synthesized 15-mer peptides to prepare specific pools and megapools (MP) to detect T-cell responses and epitope identification. CD4 and CD8 T-cell responses were detected by activation-induced cell marker (AIM) assay. Results Our study established recognition of a set of CMV potential vaccine candidates for human CD4 and CD8 T-cell responses. Our results showed vigorous poly-antigenic responses of CMV ORFs varying in their CD4+ and CD8+ reactivity. A total of 552 different epitopes (458 CD4 epitopes and 94 CD8 epitopes) were identified. Of those, 66 CD4 epitopes and 36 CD8 epitopes were recognized in 3 or more donors. Correlation between regions containing CD4 and CD8 epitopes indicates that immunogens targeting both CD4 and CD8 responses can be designed. Antigen and epitope sequences are well conserved in human CMV strains (HCMV), but poorly conserved in other beta herpesviruses. The overall CD4/CD8 activity is correlated to IgG titers that are specific to pre- and post-fusion glycoprotein (gB). We have selected epitopes from ORFs associated with significant positive associations with IgG titers. Our proposed vaccine construct contained murine epitopes to assess for immunogenicity in mice for T-cells and antibody response enhancement. Conclusion Our study identified of a set of CMV regions eliciting human CD4/CD8 memory responses and IgG responses derived from a wide breadth of different antigenic targets. These regions could be combined to elicit robust humoral and T-cell responses targeting human CMV. Funding Source Advanced Research Projects Agency for Health (ARPA-H) Topic Categories Vaccines and Immunotherapy (VAC)

Abstract Introduction Arenaviruses represent a rapidly expanding group of rodent-borne emerging human pathogens with significant pandemic potential. Diseases caused by these viruses, such as the Old-World Arenavirus (OWA) Lassa virus (LASV), which causes Lassa Fever, and the New-World Arenavirus (NWA) Junin virus (JUNV), which causes hemorrhagic fevers, currently lack effective therapeutics or vaccines. Members of the Arenaviridae family possess bi- or tri-segmented genomes encoding three to four viral proteins: glycoprotein (GP), nucleoprotein (NP), RNA polymerase (L) and matrix protein (Z). A robust T-cell immune response is critical for viral clearance and for limiting disease severity during the early stages of the infection. Methods Using a primary in vitro immunogenicity assay, we identified Conserved T cell Epitope Regions (CTERs) derived from conserved sequences within OWA and NWA, using LASV and JUNV as respective prototypes. These CTER epitopes were strongly recognized by human CD4+ T cells in vitro and were predicted to provide broad population coverage across diverse ethnicities. CTER constructs were designed based on the number of viral proteins included (GP+N+L, N+L, or L) and were assembled using AlphaFold into stable and unstable forms. Plasmids for OWA and NWA were codon-optimized and subsequently packaged into mRNA constructs. Results Our ongoing BDF1 mouse studies demonstrate that the CTER-based T-cell vaccine is both safe and immunogenic, as assessed using a combined activation-induced marker (AIM) and intracellular cytokine (ICS) assay. AIM+ T cells isolated from the spleen and lymph nodes show strong cross-reactive potential across the Arenaviridae family. Conclusion With further in vitro and in vivo evaluation, this work represents an initial step toward the development of a pan-arenavirus T-cell vaccine. Funding Source CEPI, NIH Topic Categories Vaccines and Immunotherapy (VAC)

Abstract Neoantigens are tumor-specific molecules arising from somatic alterations in cancer cells and have garnered significant interest due to their immunogenic potential. Consequently, numerous computational pipelines have been developed to identify these targets. However, systematic comparisons between neopeptide generation tools are lacking, and there is no consensus on how to handle different mutation types.To address this gap, we compared the neopeptide sequences generated by four widely used tools: the Mutated Peptide Generator (MPG) from the Cancer Epitope Database and Analysis Resource (CEDAR), the Personalized Variant Antigens by Cancer Sequencing (pVACseq), the Mutated Peptide eXtractor and Informer (MuPeXI), and the Neoantigen Prediction Pipeline (NeoPredPipe). We applied these tools to somatic mutations from the Catalogue of Somatic Mutations in Cancer (COSMIC) v102 and validated the results with experimentally validated neoantigens curated in the CEDAR database.In total, 25% of the COSMIC mutations were considered by at least one method to generate neopeptides. The methods showed considerable variability, as only 22% of the neopeptides were generated by all tools. Overall, 29% of the discrepancies in neopeptide generation were attributed to different criteria used to select mutations or transcripts for downstream analysis. The remaining discrepancies were caused by differences in the algorithms used to handle and modify reference sequences into mutated neopeptides. Experimentally validated neoepitopes from CEDAR comprised only 0.005% of the total generated neopeptides. While most neoepitopes were accurately generated by the four methods, 10% were not consistently identified across the tools.These findings underscore the need for methodological standardization to ensure reliable and reproducible neoantigen discovery. To our knowledge, this is the first comprehensive evaluation of neoantigen pipelines focused specifically on neopeptide sequence generation. Citation Format: Ibel Carri, Angela Frentzen Worley, Ashmitaa Logandha Ramamoorthy Premlal, Gauri Renjith, Malachi Griffith, Jason Greenbaum, Alessandro Sette, Bjoern Peters, Zeynep Kosaloglu-Yalcin. A comparative study of neoantigen discovery pipelines uncovers discrepancies in the generation of mutated neopeptide sequences [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB161.

Mammarenaviruses are classified into Old World and New World viruses (Old World arenaviruses [OWAs] and New World arenaviruses [NWAs]). Characterization of antigens recognized by human T cells is essential for identifying immunodominant targets, informing vaccine design, and performing immunological assessments. Here, we select the Lassa virus (LASV) as a prototype OWA to map the human CD4 T cell epitope repertoire. We then calculate conservation in different LASV lineages and other representative OWAs and NWAs and define conserved T cell epitope regions (CTERs) using Lassa as the OWA prototype and Junin as the NWA prototype. We show that these CTERs are able to broadly cross-recognize other OWA or NWA sequences. We validate our findings in humans immunized with an experimental glycoprotein complex (GPC) LASV vaccine or infected with lymphocytic choriomeningitis mammarenavirus (LCMV), as well as in the mouse model immunized with a stabilized GPC vaccine candidate. Our results on mammarenavirus-specific T cell immunity contribute to guiding the development of next-generation mammarenavirus vaccines.

Phosphorylated peptides presented by human leukocyte antigen (HLA) class II molecules play pivotal roles in immune regulation, yet their characterization and prediction remain challenging due to data noise and limited HLA coverage. Here, we introduce NetMHCIIphosPan, a prediction method for HLA-II antigen presentation of phosphorylated peptides, developed using mass spectrometry (MS)-based immunopeptidomics data sets. Employing a refined peptide identification workflow, we reanalyzed earlier HLA-II phospholigand data sets and trained predictive models, achieving superior performance compared to models trained on the original data. Binding motif analysis revealed that HLA-specific preferences for phospholigands closely aligned with those of unmodified ligands. Incorporating unmodified ligands into training further enhanced predictive accuracy, particularly for HLA-DP and HLA-DQ molecules. NetMHCIIphosPan outperformed existing tools, such as NetMHCIIpan-4.3 and MixMHC2pred-1.3, for prediction of HLA antigen presentation of phosphorylated peptides, demonstrating robustness and utility. This work establishes NetMHCIIphosPan as a state-of-the-art tool for understanding the HLA-II phospholigandome, with potential applications in immunotherapy and vaccine design.

While natural infections expose the immune system for days to weeks of inflammation and antigen presentation, immunizations with conventional bolus vaccines often lead to rapid clearance of antigens and adjuvants. Prolonged exposure to vaccines using controlled delivery devices or repeated dosing regimens has been shown to enhance germinal center reactions, leading to improved humoral responses, including increased magnitude of antibody titers and enhanced neutralizing activity. Herein, we report the use of injectable polymer-nanoparticle (PNP) hydrogels as a vaccine depot technology for sustained delivery of the clinically relevant SARS-CoV-2 Hexapro subunit antigen and a toll-like receptor agonist adjuvant. In mice, we demonstrated that PNP hydrogel vaccines enhanced germinal center responses and antibody responses relative to bolus vaccination. In nonhuman primates, hydrogel vaccines induced enhanced and durable antibody responses against wildtype and variants of concern such as Omicron BA.5 compared to bolus vaccination. We report the first use of a biomaterials-based approach for sustained delivery of vaccines in nonhuman primates, further advancing toward clinical translation.

Objectives: This study was designed to assess the safety and immunogenicity of the first dose of the TAK-003 dengue vaccine. The immune response profiles of vaccinated participants were compared among individuals who experienced or did not experience natural dengue infection in the past or as an acute infection. Methods: In this single-centre prospective observational study, subjects were stratified into three groups: Group1-dengue seronegative; Group2-dengue seropositive; Group3-acute dengue infection. The assessments of vaccine-induced immunogenicity included: DENV-2 neutralizing antibodies, monocyte and dendritic cell (DC) phenotyping and T-cell response at baseline (T0) and 3 months (T3) post-vaccination (Group1 and 2) or post-infection (Group3). Results: One hundred fifty subjects were enrolled at T0, and among them 80 subjects (median age 38 years, 50% male) were also evaluated at T3. Anti-DENV-2 neutralizing antibodies increased 26.9-and 9.19-fold in Group1 and 2, and 3.06-fold in Group3. Group1 showed increased monocytes and Group3 had reduced myeloid-DC and higher plasmacytoid-DC. Group1 and 2 exhibited DENV CD4 MP-induced T-cell responses similar to those observed in Group3. Notably, Group1 demonstrated a significantly greater T-cell response to the DENV CD8 MP than Group3. Conclusions: Preliminary data showed that TAK-0 03 vaccine is safe and immunogenic. The first vaccine dose elicits a functional antibody and a robust T-cell response. Further analyses on the current cohort are ongoing. (c) 2026 The Author(s). Published by Elsevier Ltd on behalf of British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (MTB), represents an important cause of morbidity and mortality worldwide for which an improved vaccine and immunodiagnostics are urgently needed. CD4+ and CD8+ T cells play an important role in host defense to TB. Definition of the immunodominant antigens recognized by these T cells is critical for improved understanding of the immunobiology of TB and for development of vaccines and diagnostics. Herein, we review antigens and epitopes recognized by classically human leukocyte antigen (HLA) class I- and class II-restricted CD4+ and CD8+ T cells in humans infected with MTB, as defined using either targeted or genome-wide approaches. We address the extent to which these antigens have been defined as immunodominant, protective, and/or specific to disease stages in humans and, with particular relevance to CD8+ T-cell recognition, whether these antigens are displayed by MTB-infected cells.

Neutralizing antibodies are considered the best surrogate markers of protection against a SARS-CoV-2 infection. However, the predictive value of these antibodies overlaps only slightly with other variants. In a case-control study, in pre-infected vaccinated patients, polyfunctional anti-Wuhan CD4+ T cell responses predicted protection against both the ancestral Wuhan strain and the distant Omicron variant, whereas CD4+ T cell responses to unrelated viruses (e.g., CMV, influenza) did not. Conversely, neutralizing antibodies to the Wuhan spike correlated with protection from Wuhan infection, but failed to predict breakthroughs with divergent variants such as Omicron. Confounding factors (age, sex, timing of sampling related to infection onset, number of booster doses) were accounted for to minimize bias. To explain these results, we observed very strong correlations between the anti-Wuhan CD4+ T cell responses and the corresponding anti-Omicron BA.1 CD4+ T cell response. CD4+ T cell responses may serve as a potential surrogate marker of protection, regardless of the variant.

Chikungunya virus (CHIKV), a single-stranded, positive-sense RNA alphavirus, is transmitted to humans by infected Aedes mosquitoes. It poses an emerging threat to public health in Aedes-endemic countries and a growing risk to travelers visiting these countries. Typical acute symptoms include fever, arthralgia, rash, myalgia, fatigue and headache. In over 40% of cases, these symptoms can progress into chronic disease, primarily characterized by debilitating arthralgia. CHIKV vaccine (Vimkunya, Bavarian Nordic) is an aluminum hydroxide-adjuvanted virus-like particle (VLP) vaccine recently approved in the United States, European Union, and United Kingdom for the prevention of CHIKV disease in individuals aged 12 years and above. Phase 3 results showed a favorable safety profile and high immunogenicity, with antibody responses starting to build as early as eight days after immunization. Here, we evaluated whether Vimkunya is also able to induce CHIKV-specific T cell responses. Responses were assessed in longitudinal clinical samples from vaccinated individuals (N = 30) at five time points (day 1 pre-immunization, and days 8, 29, 57, and 182 post-immunization) using activation-induced marker (AIM) assays. Comparable to the antibody responses, CHIKV-specific CD4+ T cells were detected as early as eight days post-vaccination, with their frequency increasing over 57 days and stabilizing until 182 days. These results support the rapid induction and durability of the immune response elicited by Vimkunya, thereby supporting this vaccine's potential to provide protection against CHIKV disease.

High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with intravesical instillations of Bacillus Calmette-Guérin (BCG), which trigger a local immune response. Improved patient outcomes have been linked to the recruitment of CD4+ T helper type 1 (Th1) cells to the bladder. However, specific antigens recognized by the bladder-infiltrating T cells remain largely unknown. In this study, we followed thirty-two patients with NMIBC undergoing BCG immunotherapy. Longitudinal blood and urine samples were collected to investigate the dynamics and characteristics of BCG-specific T cells. We detected pre-existing BCG-specific CD4+ T cells in most BCG therapy-naive patients before treatment induction. BCG immunotherapy increased the frequency and memory differentiation of circulating BCG-specific CD4+ T cells, which displayed a polyfunctional Th1 phenotype. Importantly, we provide evidence that BCG-specific CD4+ Th1 cells can be detected in urine during therapy, suggesting their recruitment to the bladder. This study provides novel biological insights into the cellular mechanisms of BCG-induced immunity in bladder cancer.

OBJECTIVES:This study was designed to assess the safety and immunogenicity of the first dose of the TAK-003 dengue vaccine. The immune response profiles of vaccinated participants were compared among individuals who experienced or did not experience natural dengue infection in the past or as an acute infection. METHODS:In this single-centre prospective observational study, subjects were stratified into three groups: Group1-dengue seronegative; Group2-dengue seropositive; Group3-acute dengue infection. The assessments of vaccine-induced immunogenicity included: DENV-2 neutralizing antibodies, monocyte and dendritic cell (DC) phenotyping and T-cell response at baseline (T0) and 3 months (T3) post-vaccination (Group1 and 2) or post-infection (Group3). RESULTS:One hundred fifty subjects were enrolled at T0, and among them 80 subjects (median age 38 years, 50% male) were also evaluated at T3. Anti-DENV-2 neutralizing antibodies increased 26.9- and 9.19-fold in Group1 and 2, and 3.06-fold in Group3. Group1 showed increased monocytes and Group3 had reduced myeloid-DC and higher plasmacytoid-DC. Group1 and 2 exhibited DENV CD4 MP-induced T-cell responses similar to those observed in Group3. Notably, Group1 demonstrated a significantly greater T-cell response to the DENV CD8 MP than Group3. CONCLUSIONS:Preliminary data showed that TAK-003 vaccine is safe and immunogenic. The first vaccine dose elicits a functional antibody and a robust T-cell response. Further analyses on the current cohort are ongoing.